Christophe Faisy

Impact of energy deficit calculated by a predictive method on outcome in medical patients requiring prolonged acute mechanical ventilation

To assess energy balance in very sick medical patients requiring prolonged acute mechanical ventilation and its possible impact on outcome, we conducted an observational study of the first 14 d of intensive care unit (ICU) stay in thirty-eight consecutive adult patients intubated at least 7 d. Exclusive enteral nutrition (EN) was started within 24 h of ICU admission and progressively increased, in absence of gastrointestinal intolerance, to the recommended energy of 125.5 kJ/kg per d. Calculated energy balance was defined as energy delivered - resting energy expenditure estimated by a predictive method based on static and dynamic biometric parameters. Mean energy balance was - 5439 (sem 222) kJ per d. EN was interrupted 23 % of the time and situations limiting feeding administration reached 64 % of survey time. ICU mortality was 72 %. Non-survivors had higher mean energy deficit than ICU survivors (P = 0.004). Multivariate analysis identified mean energy deficit as independently associated with ICU death (P = 0.02). Higher ICU mortality was observed with higher energy deficit (P = 0.003 comparing quartiles). Using receiver operating characteristic curve analysis, the best deficit threshold for predicting ICU mortality was 5021 kJ per d. Kaplan-Meier analysis showed that patients with mean energy deficit > or =5021 kJ per d had a higher ICU mortality rate than patients with lower mean energy deficit after the 14th ICU day (P = 0.01). The study suggests that large negative energy balance seems to be an independent determinant of ICU mortality in a very sick medical population requiring prolonged acute mechanical ventilation, especially when energy deficit exceeds 5021 kJ per d.

Intranasal drug delivery: an efficient and non-invasive route for systemic administration: focus on opioids.

Intranasal administration is a non-invasive route for drug delivery, which is widely used for the local treatment of rhinitis or nasal polyposis. Since drugs can be absorbed into the systemic circulation through the nasal mucosa, this route may also be used in a range of acute or chronic conditions requiring considerable systemic exposure. Indeed, it offers advantages such as ease of administration, rapid onset of action, and avoidance of first-pass metabolism, which consequently offers for example an interesting alternative to intravenous, subcutaneous, oral transmucosal, oral or rectal administration in the management of pain with opioids. Given these indisputable interests, fentanyl-containing formulations have been recently approved and marketed for the treatment of breakthrough cancer pain. This review will outline the relevant aspects of the therapeutic interest and limits of intranasal delivery of drugs, with a special focus on opioids, together with an in-depth discussion of the physiological characteristics of the nasal cavity as well as physicochemical properties (lipophilicity, molecular weight, ionisation) and pharmaceutical factors (absorption enhancers, devices for application) that should be considered for the development of nasal drugs.

Clinically significant gastrointestinal bleeding in critically ill patients with and without stress-ulcer prophylaxis

ObjectiveTo compare the rates of clinically significant gastrointestinal bleeding and the number of blood units and endoscopies required for gastrointestinal hemorrhage between patients receiving or not receiving stress-ulcer prophylaxis.DesignHistorical observational study comparing two consecutive periods: with (phase 1) and without stress-ulcer prophylaxis (phase 2).Design and settingA 17-bed intensive care unit in a university teaching hospital.PatientsIn phase 1 there were 736 patients and in phase 2 737. Those in the two phases were comparable in age and reason for admission; clinically significant gastrointestinal bleeding rates did not differ between the two phases, but patients in phase 2 were more severely ill.Measurements and resultsComparable numbers of blood units were transfused per bleeding patient in the two phases, especially for patients with significant gastrointestinal bleeding. During each phase 19 fibroscopies were performed for significant bleeding, and two patients required surgery. The clinically significant gastrointestinal bleeding rate and outcome did not differ in patients with at least one risk factor. Total expenditures directly related to gastrointestinal bleeding were similar during the two phases; the total cost incurred by stress-ulcer prophylaxis was estimated at €6700.ConclusionsOur results suggest that stress-ulcer prophylaxis does not influence the clinically significant gastrointestinal bleeding rate in intensive care unit patients or the cost of its management.

Ultrasonographic Diagnostic Criterion for Severe Diaphragmatic Dysfunction After Cardiac Surgery

BACKGROUND Severe diaphragmatic dysfunction can prolong mechanical ventilation after cardiac surgery. An ultrasonographic criterion for diagnosing severe diaphragmatic dysfunction defined by a reference technique such as transdiaphragmatic pressure measurements has never been determined. METHODS Twenty-eight patients requiring mechanical ventilation > 7 days postoperatively were studied. Esophageal and gastric pressures were measured to calculate transdiaphragmatic pressure during maximal inspiratory effort and the Gilbert index, which evaluates the diaphragm contribution to respiratory pressure swings during quiet ventilation. Ultrasonography allowed measuring right and left hemidiaphragmatic excursions during maximal inspiratory effort. Best E is the greatest positive value from either hemidiaphragm. Twenty cardiac surgery patients with uncomplicated postoperative course were also evaluated with ultrasonography preoperatively and postoperatively. Measurements were performed in semirecumbent position. RESULTS Transdiaphragmatic pressure during maximal inspiratory effort was below normal value in 27 of the 28 patients receiving prolonged mechanical ventilation (median, 39 cm H(2)O; interquartile range [IQR] 28 cm H(2)O). Eight patients had Gilbert indexes <or= 0 indicating severe diaphragmatic dysfunction. Best E was lower in patients with Gilbert index <or= 0 than > 0 (30 mm; IQR, 10 mm; vs 19 mm; IQR, 7 mm, respectively; p = 0.001). Best E < 25 mm had a positive likelihood ratio of 6.7 (95% confidence interval [CI], 2.4 to 19) and a negative likelihood ratio of 0 (95% CI, 0 to 1.1) for having a Gilbert index <or= 0. None of the patients with uncomplicated course had Best E < 25 mm either preoperatively or postoperatively. CONCLUSIONS Ultrasonographic-based determination of hemidiaphragm excursions in patients requiring prolonged mechanical ventilation after cardiac surgery may help identify those with and without severe diaphragmatic dysfunction as defined by the Gilbert index.

Impact of Morbidity and Mortality Conferences on Analysis of Mortality and Critical Events in Intensive Care Practice

BACKGROUND Morbidity and mortality conferences are a tool for evaluating care management, but they lack a precise format for practice in intensive care units. OBJECTIVES To evaluate the feasibility and usefulness of regular morbidity and mortality conferences specific to intensive care units for improving quality of care and patient safety. METHODS For 1 year, a prospective study was conducted in an 18-bed intensive care unit. Events analyzed included deaths in the unit and 4 adverse events (unexpected cardiac arrest, unplanned extubation, reintubation within 24-48 hours after planned extubation, and readmission to the unit within 48 hours after discharge) considered potentially preventable in optimal intensive care practice. During conferences, events were collectively analyzed with the help of an external auditor to determine their severity, causality, and preventability. RESULTS During the study period, 260 deaths and 100 adverse events involving 300 patients were analyzed. The adverse events rate was 16.6 per 1000 patient-days. Adverse events occurred more often between noon and 4 pm (P = .001).The conference consensus was that 6.1% of deaths and 36% of adverse events were preventable. Preventable deaths were associated with iatrogenesis (P = .008), human errors (P < .001), and failure of unit management factors or communication (P = .003). Three major recommendations were made concerning standardization of care or prescription and organizational management, and no similar incidents have recurred. CONCLUSION In addition to their educational value, regular morbidity and mortality conferences formatted for intensive care units are useful for assessing quality of care and patient safety.

Clinical pharmacokinetics and pharmacodynamics of desloratadine, fexofenadine and levocetirizine : a comparative review.

Second-generation histamine H1 receptor antagonists were developed to provide efficacious treatment of allergic rhinitis (AR) and chronic idiopathic urticaria (CIU) while decreasing adverse effects associated with first-generation agents. When comparing the efficacy and safety profiles of the newest second-generation antihistamines — desloratadine, fexofenadine and levocetirizine — many pharmacological and clinical criteria must be considered. Most importantly, these elements should not be evaluated separately but, rather, as parts of a puzzle that create a whole picture. As a class, second-generation antihistamines are highly selective for the H1 receptor. Some bind to it with high affinity, although there is marked heterogeneity among the various compounds. They have a limited effect on the CNS, and clinical studies have noted almost no significant drugdrug interactions in the agents studied. No major cytochrome P450 inhibition has been reported with desloratadine, fexofenadine and levocetirizine, and the bioavailability of desloratadine is minimally affected by drugs interfering with transporter molecules. Of the second-generation antihistamines, desloratadine has the greatest binding affinity for the H1 receptor. The use of desloratadine, fexofenadine and levocetirizine is not associated with clinically relevant antimuscarinic effects. Desloratadine and fexofenadine do not impair cognitive or psychomotor functioning and are comparable with placebo in terms of somnolence. Based on these pharmacological characteristics, as well as clinical endpoints such as symptom scores, quality-of-life surveys, inflammatory cell counts and investigators’ global evaluations, we conclude that desloratadine, fexofenadine and levocetirizine are all efficacious treatments for AR and CIU. However, differences among the antihistamines in relation to a lack of significant interaction with drug transporter molecules and somnolence in excess of placebo may provide some advantages for the overall profile of desloratadine compared with fexofenadine and levocetirizine.

Validation of a predictive method for an accurate assessment of resting energy expenditure in medical mechanically ventilated patients.

Objective:Use comparison with indirect calorimetry to confirm the ability of our previously described equation to predict resting energy expenditure in mechanically ventilated patients. Design:Prospective, validation study. Setting:Eighteen-bed, medical intensive care unit at a teaching hospital. Patients:All adult patients intubated >24 hrs were assessed for eligibility. Exclusion criteria were clinical situations that could contribute to erroneous calorimetric measurements. Interventions:Resting energy expenditure was calculated using the original Harris-Benedict equations and those corrected for usual stress factors, the Swinamer equation, the Fusco equation, the Ireton-Jones equation, and our equation: resting energy expenditure (kcal/day) = 8 × weight (kg) + 14 × height (cm) + 32 × minute ventilation (L/min) + 94 × temperature (°C) − 4834. Measurements and Main Results:Resting energy expenditure was measured by indirect calorimetry for the 45 included patients. Resting energy expenditure calculated with our predictive model correlated with the measured resting energy expenditure (r2 = .62, p < .0001), and Bland-Altman analysis showed a mean bias of −192 ± 277 kcal/day, with limits of agreement ranging from −735 to 351 kcal/day. Resting energy expenditure calculated with the Harris-Benedict equations was more weakly correlated with measured resting energy expenditure (r2 = .41, p < .0001), with Bland-Altman analysis showing a mean bias of 279 ± 346 kcal/day between them and the limits of agreement ranging from −399 to 957 kcal/day. Applying usual stress-correction factors to the Harris-Benedict equations generated wide variability, and the correlation with measured resting energy expenditure was poorer (r2 = .18, p < .0001), with Bland-Altman analysis showing a mean bias of −357 ± 750 kcal/day and limits of agreement ranging from −1827 to 1113 kcal/day. The use of the Swinamer, Fusco, or Ireton-Jones predictive methods yielded weaker correlation between calculated and measured resting energy expenditure (r2 = .41, p < .0001; r2 = .38, p < .0001; r2 = .39, p < .0001, respectively) than our equation, and Bland-Altman analysis showed no improvement in agreement and variability between methods. Conclusions:The Faisy equation, based on static (height), less stable (weight), and dynamic biometric variables (temperature and minute ventilation), provided precise and unbiased resting energy expenditure estimations in mechanically ventilated patients.

Early-onset ventilator-associated pneumonia in adults randomized clinical trial: comparison of 8 versus 15 days of antibiotic treatment.

Purpose The optimal treatment duration for ventilator-associated pneumonia is based on one study dealing with late-onset of the condition. Shortening the length of antibiotic treatment remains a major prevention factor for the emergence of multiresistant bacteria. Objective To demonstrate that 2 different antibiotic treatment durations (8 versus 15 days) are equivalent in terms of clinical cure for early-onset ventilator-associated pneumonia. Methods Randomized, prospective, open, multicenter trial carried out from 1998 to 2002. Measurements The primary endpoint was the clinical cure rate at day 21. The mortality rate was evaluated on days 21 and 90. Results 225 patients were included in 13 centers. 191 (84.9%) patients were cured: 92 out of 109 (84.4%) in the 15 day cohort and 99 out of 116 (85.3%) in the 8 day cohort (difference = 0.9%, odds ratio = 0.929). 95% two-sided confidence intervals for difference and odds ratio were [−8.4% to 10.3%] and [0.448 to 1.928] respectively. Taking into account the limits of equivalence (10% for difference and 2.25 for odds ratio), the objective of demonstrative equivalence between the 2 treatment durations was fulfilled. Although the rate of secondary infection was greater in the 8 day than the 15 day cohort, the number of days of antibiotic treatment remained lower in the 8 day cohort. There was no difference in mortality rate between the 2 groups on days 21 and 90. Conclusion Our results suggest that an 8-day course of antibiotic therapy is safe for early-onset ventilator-associated pneumonia in intubated patients. Trial Registration ClinicalTrials.gov NCT01559753

Assessment of body cell mass at bedside in critically ill patients

Critical illness affects body composition profoundly, especially body cell mass (BCM). BCM loss reflects lean tissue wasting and could be a nutritional marker in critically ill patients. However, BCM assessment with usual isotopic or tracer methods is impractical in intensive care units (ICUs). We aimed to modelize the BCM of critically ill patients using variables available at bedside. Fat-free mass (FFM), bone mineral (Mo), and extracellular water (ECW) of 49 critically ill patients were measured prospectively by dual-energy X-ray absorptiometry and multifrequency bioimpedance. BCM was estimated according to the four-compartment cellular level: BCM = FFM - (ECW/0.98) - (0.73 × Mo). Variables that might influence the BCM were assessed, and multivariable analysis using fractional polynomials was conducted to determine the relations between BCM and these data. Bootstrap resampling was then used to estimate the most stable model predicting BCM. BCM was 22.7 ± 5.4 kg. The most frequent model included height (cm), leg circumference (cm), weight shift (Δ) between ICU admission and body composition assessment (kg), and trunk length (cm) as a linear function: BCM (kg) = 0.266 × height + 0.287 × leg circumference + 0.305 × Δweight - 0.406 × trunk length - 13.52. The fraction of variance explained by this model (adjusted r(2)) was 46%. Including bioelectrical impedance analysis variables in the model did not improve BCM prediction. In summary, our results suggest that BCM can be estimated at bedside, with an error lower than ±20% in 90% subjects, on the basis of static (height, trunk length), less stable (leg circumference), and dynamic biometric variables (Δweight) for critically ill patients.

Roflumilast inhibits the release of chemokines and TNF-α from human lung macrophages stimulated with lipopolysaccharide

BACKGROUND AND PURPOSE Lung macrophages are critically involved in respiratory diseases. This study assessed the effects of the PDE4 inhibitor roflumilast and its active metabolite, roflumilast N‐oxide on the release of a range of chemokines (CCL2, 3, 4, CXCL1, 8, 10) and of TNF‐α, from human lung macrophages, stimulated with bacterial lipopolysaccharide LPS.